| First Author | Habib GM | Year | 2007 |
| Journal | Free Radic Biol Med | Volume | 42 |
| Issue | 2 | Pages | 191-201 |
| PubMed ID | 17189825 | Mgi Jnum | J:117265 |
| Mgi Id | MGI:3695876 | Doi | 10.1016/j.freeradbiomed.2006.10.036 |
| Citation | Habib GM, et al. (2007) Glutathione protects cells against arsenite-induced toxicity. Free Radic Biol Med 42(2):191-201 |
| abstractText | To understand the role of glutathione (GSH) in the protection of cells from arsenite toxicity, we studied the mechanism of apoptotic cell death in cells genetically unable to synthesize GSH (GCS-2 cells). Arsenite stimulated an increase in protein ubiquitination in GCS-2 cells while the wild-type cells were unaffected. Arsenite treatment increased lipid peroxidation and induced ubiquitination of molecular chaperone Hsp90 and impaired its ability to bind cochaperone p50(Cdc-37) and client proteins Plk-1 and Cdk-4 in GCS-2 cells. Treatment with arsenite also partially inhibited proteasome activity in GCS-2 cells. In these cells stably transfected with GFP(u) (a reporter consisting of a short degron fused to the COOH-terminus of GFP), intracellular fluorescence increased, suggesting the accumulation of GFP aggregates. GCS-2 cells underwent apoptosis accompanied by release of cytochrome c into the cytoplasm. Taken together, these data suggest that a possible mechanism of arsenite-induced apoptosis is the accumulation of ubiquitinated proteins and impairment of the protein degradative pathway. Further, protection from arsenite-induced ubiquitination is mediated by GSH and to a lesser extent by available reducing equivalents in the cells. |
